Effects of development and hypoxia on glutamate transporters in rat brains

The rapid clearance of extracellular glutamate into neurons and glia by glutamate transporters contributes to the termination of the excitatory signal and the protection of neurons from excitotoxic injury. Since 1) hypoxic neuronal injury could be related in part to extracellular glutamate accumulation and 2) neuronal tolerance to hypoxic stress is different between the immature and adult brain, we have hypothesized that glutamate transporter level is different at different ages and is differentially regulated in the immature and adult brain during hypoxia. To test our hypothesis, we used western blotting to examine glutamate transporter expression in developing and hypoxia-exposed (FiO₂=9±0.5%) rat brains The data show that 1) EAAC1 (a neuronal glutamate transporter) was more abundant than GLT-1 (a glial glutamate transporter) in fetal brain (E21), reached peak levels (>200% of fetal level) between P8 and P13, and then decreased to adult levels (60% of fetal level); in contrast, the level of GLT-1 was extremely low at birth and increased with age until adulthood (>5-fold higher than the fetal level); and 2) EAAC1 was up-regulated in newborn brains exposed to hypoxia for 5-10 days (starting from P3), especially in the cortex (e.g., doubled for 10-day hypoxia); but did not increase in adult brains exposed to hypoxia for the same periods (starting from P90). Our results suggest that neuronal glutamate transporters are more in immature than in adult brain and can further increase in response to hypoxic stress.